Wound healing is a process of regenerating dermal and epidermal tissues to repair a wound. This process is complex, involving several phases, such as the vascular reaction and blood clotting, inflammatory, proliferative and remodeling phases. These phases overlap and are partly mutually dependent, so that the sequence only approximately corresponds to the time course of wound healing.
The vascular reaction prevents major blood losses and entails vasoconstriction, which persists until blood clotting provisionally closes the wound. In the inflammatory phase, increased numbers of blood cells such as granulocytes, macrophages and lymphocytes, are brought to the area at or near the wound. The blood cells clean the wound by taking up exogenous materials and tissue detritus and breaking them down enzymatically.
Collagen deposition, granulation tissue formation, epithelialization and wound contraction occur in the proliferative phase. For example, new blood vessels are formed (angiogenesis) from as early as the third day after the injury to provide adequate blood supply for wound healing. New connective tissue formation takes place in parallel with the vascularization. Fibroblasts migrate along the fibrin matrix into the wound. They produce the connective tissue ground substance consisting of proteoglycans and collagen fibers, which are crucial for tissue strength. In the maturation and remodeling phase, collagen fibers are remodeled and realigned along tension lines and cells that are no longer needed are removed by apoptosis.
Scars are areas of fibrous tissue that replace normal tissues destroyed by a wound. Scar tissue is not identical to the normal tissue and is often of inferior functional quality. For example, scars in the skin can be less resistant to ultraviolet radiation, and may contain no sweat glands and hair follicles. Importantly, scar tissue never achieves the essential flexibility of normal epidermal tissue and therefore presents not only cosmetic issues but also chronic mechanical problems. Scarring is a natural part of the wound healing process. With the exception of very minor lesions, every wound (e.g. after accident, disease, or surgery) results in some degree of scarring.
Wound healing requires a balanced equilibrium of contrary actions such as cell proliferation and cell apoptosis, construction and breakdown of blood vessels, and construction and breakdown of collagen. Disturbance of the equilibrium may lead to the formation of chronic wounds, which may never heal or heal at slower rate, and/or increased scar formation. Also, “permanentized” scar tissue composed of fibroblastic cells may form, which frequently results in keloids, a type of scar resulting from an overgrowth of tissue at the site of a healed skin injury. Keloids are unsightly and problematic firm surface tissue of different coloration and different and poorer qualities. They are rubbery lesions or shiny, fibrous nodules, having a color from pink to flesh-colored or red to dark brown in color.
There is a continuing need for a novel, simple and reproducible wound healing therapy to improve wound healing and reduce symptoms associated with wound, such as pain and scar formation, during the wound healing process. Preferably such therapy involves a therapeutic agent that is stable over time, relatively inexpensive to prepare, and achieves its wound healing effects with dose regimens that are associated with minimal toxicity.